Topical Management of Peristomal Pyoderma Gangrenosum: A Report of 3 Case Studies.

BACKGROUND: Peristomal pyoderma gangrenosum (PPG) presents multiple challenges for healthcare providers. The diagnosis of PPG may be delayed, and it may be mistaken for an irritant dermatitis or an infection. Patients with ostomies secondary to inflammatory bowel disease (IBD) may experience PPG. Issues related to PPG include difficulty maintaining a seal of the ostomy pouching system and preventing contamination of the painful, necrotic ulcerations characteristic of this condition. Treatment focuses on the appropriate assessment of the ulcers, successful pouch application, and proper management of IBD through a collaborative effort of both dermatologists and certified WOC nurses (CWOCN). CASES: We treated 3 patients diagnosed with Crohn's disease (CD) who developed refractory PPG. All 3 were treated with a topical steroid lotion, prednisone, and adalimumab or a combination of these agents. Ostomy products and application were tailored to prevent leakage and protect areas of ulceration. All ulcers were healed within 6 months of our initial consultation. CONCLUSION: We successfully managed 3 patients with CD and PPG with appropriate ostomy care, including revision of the ostomy pouching techniques, topical steroid treatment, and treatment based on assessment of ulcer status by the dermatologist and the WOC nurse.

Case of Subarachnoid Hemorrhage from Ruptured Oncotic Fusiform Aneurysms from Choriocarcinoma Metastasis Treated with Aneurysmectomy and Vessel Reconstruction.

BACKGROUND: Oncotic aneurysm is a rare condition with a high mortality rate. Because no consensus has been reached regarding therapeutic strategy for ruptured oncotic aneurysm, treatment remains challenging. CASE DESCRIPTION: A 35-year-old woman developed sudden onset of severe headache. Computed tomography showed subarachnoid hemorrhage and cerebral angiography revealed 2 fusiform aneurysms in the distal portion of the left middle cerebral artery. Aneurysmectomy with vessel reconstruction using a superficial temporal artery graft was performed to maintain blood flow to the distal middle cerebral artery. Pathologic examination of the aneurysm and wall of the resected recipient middle cerebral artery showed infiltrating trophoblasts. Immunostaining for human chorionic gonadotropin was positive in the aneurysm specimen. On the basis of an elevated concentration of serum human chorionic gonadotropin, choriocarcinoma with ruptured intracranial oncotic aneurysms was diagnosed. After further systemic examination for carcinoma, chemotherapy was initiated. CONCLUSIONS: Aneurysmectomy, resection of the parent artery with irregular walls and reconstruction to the distal recipient artery with normal intima should be considered to secure patency of the anastomosis and prevent the recurrence of oncotic aneurysm. Subsequent chemotherapy is essential to prevent carcinomatous meningitis and disease progression.

Association between leptin gene expression in subcutaneous adipose tissue and circulating leptin levels in obese patients with psoriasis.

Numerous reports have shown that psoriasis is associated with obesity and leptin. However, few reports are available on the association between serum leptin levels and leptin gene expression in SAT of psoriasis patients. To clarify this point, we examined serum leptin levels and expression levels of leptin messenger RNA (mRNA) in subcutaneous adipose tissue (SAT) of psoriasis patients. 17 psoriasis vulgaris patients and 6 non-obese control patients who underwent skin surgery were enrolled in this study. We measured serum leptin levels. SAT samples in psoriasis patients were taken from beneath the lesional psoriatic skin at the time of skin biopsy. Leptin mRNA expression in SAT was measured using quantitative real-time reverse transcription polymerase chain reaction (real-time RT-PCR) amplification. Leptin mRNA expression showed a positive correlation with serum leptin levels and BMI. We classified psoriasis patients into two groups according to BMI: the group of non-obese psoriasis patients (BMI < 25, n = 7), and the group of obese psoriasis patients (BMI ≥ 25, n = 10). PASI score, serum leptin levels and Leptin mRNA expression in SAT were significantly higher in the obese psoriasis patients than in the non-obese psoriasis patients. Leptin mRNA expression in SAT was correlated with circulating levels of leptin, the severity of psoriasis, and obesity in psoriasis patients. Serum leptin levels and leptin mRNA expression levels in SAT of non-obese psoriasis patients were not significantly different from those of non-obese controls. The altered secretion of leptin by SAT may be related to the severity of psoriasis.

Feature on erythropoiesis in dietary restricted rats.

We attempted to characterize the influence of undernutrition on erythropoiesis in toxicity studies. Male rats were divided into the following 5 groups: dietary restriction groups in which feeding was restricted by 33% or 66% for 14 days (R33 and R66); phlebotomy groups in which 1% or 4% of total blood volume was removed by serial phlebotomy for 14 days (PB01 and PB04); and a nontreated group (NT). Toxicological parameters such as hematology and blood chemistry were evaluated. The body weight gains in the R33 and phlebotomy groups (PB01 and PB04) were similar and were less than that observed in the NT group. Decreases in peripheral blood reticulocytes, bone marrow erythroids and the unsaturated iron binding capacity (UIBC) were observed as changes that suppressed erythropoiesis in the R33 and R66 groups. However, increases in reticulocytes and UIBC were observed as opposite changes in the phlebotomy groups. In addition, an increase in the blood urea nitrogen level and a decrease in the serum alkaline phosphatase level were observed as changes reflecting poor nutrition in the phlebotomy groups. Decreased reticulocytes which are related to poor nutrition were not observed. However, increases in those cells as reflected by a loss of blood were observed in the phlebotomy groups. Even if undernutrition suppresses erythropoiesis, the ability of erythropoiesis to respond to a demand appears to be retained. In repeated dose toxicity studies, decreased food consumption is often observed in the drug administration groups. Our study results provide useful information for hematological evaluations in toxicity studies.

Evaluation of myelotoxicity in dietary restricted rats.

The purpose of this study was to clarify the effect of decreased food consumption on evaluation of myelotoxicity in routine general toxicity studies. Male rats were divided into the following 7 groups: 12, 15, and 18 mg/kg 5-fluorouracil (5-FU) treatment groups (FU12, FU15 and FU18); dietary restriction groups (R12, R15 and R18 receiving the same amount of food as the rats in the FU12, FU15 and FU18 groups, respectively); and a nontreated control group (NT). We compared the changes in body weight, hematology and the results of cytological analyses of bone marrow and histopathology among the groups after administration and recovery periods of 14 and 7 days, respectively. At the end of the administration period, the FU15 and FU18 groups showed decreases in many hematologic and bone marrow parameters that were all similar to those in the corresponding dietary restriction groups (R15 and R18). A granulocyte abnormality (polyploidy: frequency of 1% or less) was also observed in all 5-FU treated groups. At the end of the recovery period, increases in the reticulocyte and platelet counts and extramedullary hematopoiesis of the spleen were observed in the 5-FU treated groups. These results indicate that the results of general toxicity studies in rats should be evaluated in consideration of dietary restriction effects when food consumption is decreased at about 30-40% or more. Careful morphological observation of hemocytes would be helpful in distinguishing the effect of a drug from that of dietary restriction in relation to hematological and bone marrow parameters. Performance of a recovery test to determine the reactive response of hematopoiesis is also recommended.

Mutations induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the lacZ and cII genes of Muta Mouse.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) found in chewing tobacco, snuff, cigarettes, and cigars is a tobacco-specific nitrosamine and classified as a possible human carcinogen (Class 2B) by the International Agency for Research on Cancer (IARC). NNK given intraperitoneally was seen to induce lung and liver adenomas. To evaluate the genotoxicity of NNK in vivo, NNK was intraperitoneally administered to Muta Mouse at two concentrations (125 and 250 mg/kg, once a week for 4 weeks) followed by the measurement of mutant frequencies in the lacZ and cII genes from lung and liver in the same mice. Characterization of the types of the mutation was determined by sequencing the cII genes from mutant plaques. The mutant frequencies in both target genes from both organs dose-dependently increased up to 10 times compared to those of the control group. For the types of mutations, the ratio of the G:C to A:T mutation in the total number of mutants was less than the ratio of A:T to T:A and A:T to C:G transversion, contrary to a previous report. The A:T to T:A transversion was the most highly induced mutation both in the lung and liver cII genes. The increasing rate of mutant frequencies in lung and liver over the vehicle control was 55 and 56 times, respectively, while the increasing rate of G:C to A:T transition was only 1.9 and 2.8 times, respectively. These observations show that NNK predominantly induces DNA adducts leading to A:T to T:A and/or A:T to C:G mutations in the transgene.

HMG-CoA reductase inhibitor, fluvastatin, has cholesterol-lowering independent "direct" effects on atherosclerotic vessels in high cholesterol diet-fed rabbits.

Recent clinical studies suggest that some of the beneficial effects of 3-hydroxy-3-metylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the incidence of myocardial infarctions and ischemic strokes may be through their non-cholesterol-lowering "direct" effects on atherosclerotic vessels. We designed this study to test the hypothesis that fluvastatin inhibits atheroma formation and increase plaque stability independent of cholesterol-lowering effects. Rabbits were fed 0.5% high-cholesterol diet for 12 weeks (progression phase) and then fed the high-cholesterol diet either containing or not containing fluvastatin 2mg/kg per day for additional 8 weeks (treatment phase). Rabbits fed normal diet were used as control. Plasma total and LDL-cholesterol concentrations did not differ during the treatment phase of the experiment. Atherosclerotic changes (plaque formation, lipid- and macrophage-rich intimal thickening, the increase in MCP-1, IL-8, TNF-alpha, IL-1beta, M-CSF, MMP-1, MMP-9, MMP-12, and ACE mRNA expression, and the increase in plasma MCP-1 levels) were observed in the high-cholesterol diet group (HC). All of these changes were less in the fluvastatin-treated group (HC+Flu) than in HC. There was no significant difference in aortic collagen (type I and type IV) mRNA expression between groups. Furthermore, fluvastatin increased the extracellular matrix content (collagen) and vascular smooth muscle cell composition in the atherosclerotic lesion, leading to the increase in plaque stability score (collagen+smooth muscle cell area)/(macrophage+lipid deposition area) in HC+Flu. Fluvastatin not only reduced atherogenesis but also to stabilized vulnerable atheromatous plaques in atherosclerotic rabbits, presumably through the macrophage recruitment and activation in the aortic lesion, at a low dose without cholesterol-lowering effects.

Detection of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic acid, teas and fruit juices.

The genotoxicity of endogenously formed N-nitrosamines from secondary amines and sodium nitrite (NaNO(2)) was evaluated in multiple organs of mice, using comet assay. Groups of four male mice were orally given dimethylamine, proline, and morpholine simultaneously with NaNO(2). The stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow were sampled 3 and 24 h after these compounds had been ingested. Although secondary amines and the NaNO(2) tested did not yield DNA damage in any of the organs tested, DNA damage was observed mainly in the liver following simultaneous oral ingestion of these compounds. The administration within a 60 min interval also yielded hepatic DNA damage. It is considered that DNA damage induced in mouse organs with the coexistence of amines and nitrite in the acidic stomach is due to endogenously formed nitrosamines. Ascorbic acid reduced the liver DNA damage induced by morpholine and NaNO(2). Reductions in hepatic genotoxicity of endogenously formed N-nitrosomorpholine by tea polyphenols, such as catechins and theaflavins, and fresh apple, grape, and orange juices were more effective than was by ascorbic acid. In contrast with the antimutagenicity of ascorbic acid in the liver, ascorbic acid yielded stomach DNA damage in the presence of NaNO(2) (in the presence and absence of morpholine). Even if ascorbic acid acts as an antimutagen in the liver, nitric oxide (NO) formed from the reduction of NaNO(2) by ascorbic acid damaged stomach DNA.

Dipeptidyl peptidase IV inhibition improves impaired glucose tolerance in high-fat diet-fed rats: study using a Fischer 344 rat substrain deficient in its enzyme activity.

This study was performed to determine the effects of a high-fat diet on glucose metabolism after an oral glucose challenge in high-fat diet-fed dipeptidyl peptidase IV (DPP-IV) positive (+) and deficient (-) Fischer 344 (F344) rats and the effects of novel DPP-IV inhibitor NVP-DPP728 (1-[2-[(5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine monohydrochloride salt) on glucose tolerance in high-fat diet-fed F344 rats. In DPP-IV(+) rats, a high-fat diet load caused impaired glucose tolerance, such as increases of plasma insulin and blood glucose concentrations after oral glucose challenge, compared with a standard chow-fed group. In contrast, no marked change in glucose tolerance was induced by the high-fat diet in DPP-IV(-) rats. Blood glucose concentrations in DPP-IV(-) rats after glucose challenge were significantly lower than in DPP-IV(+) rats under high-fat diet load conditions. In standard chow and high-fat diet-fed DPP-IV(+) rats, NVP-DPP728 significantly suppressed glucose excursions after glucose challenge by inhibiting the plasma DPP-IV activity, associated with the stimulation of early insulin secretion. NVP-DPP728 did not affect glucose tolerance in DPP-IV(-) rats under both conditions. These results indicate that the amelioration of glucose tolerance by NVP-DPP728 in DPP-IV(+) rats was directly due to the inhibition of plasma DPP-IV activity, which might be via the subsequent increase in endogenous incretin action.

Dipeptidyl peptidase IV inhibitor NVP-DPP728 ameliorates early insulin response and glucose tolerance in aged rats but not in aged Fischer 344 rats lacking its enzyme activity.

The aim of this study was to investigate the effects of aging on glucose metabolism after oral glucose challenge in aged dipeptidyl peptidase IV (DPP-IV) positive (+) Fischer 344 (F344), DPP-IV deficient (-) F344 and DPP-IV(+) Wistar rats and to determine the effect of a DPP-IV inhibitor NVP-DPP728 (1-[2-[(5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine monohydrochloride salt) on glucose tolerance in aged rats. Aging caused a decrease in early insulin response after an oral glucose challenge in aged Wistar or DPP-IV(+) F344 rats, but not in aged DPP-IV(-) F344 rats, compared with young control groups. Glucose tolerance after an oral glucose challenge in aged DPP-IV(-) F344 rats was better than in aged DPP-IV(+) F344 and Wistar rats associated with the preservation of the early insulin response. NVP-DPP728 improved the glucose tolerance after an oral glucose challenge by potentiating the early insulin response throughout the inhibition of plasma DPP-IV activity in aged DPP-IV(+) Wistar and F344 rats. In contrast, NVP-DPP728 did not affect the glucose tolerance after an oral glucose challenge in aged DPP-IV(-) F344 rats. These results indicate that treatment with NVP-DPP728 ameliorated glucose tolerance in aged rats by the direct inhibition of plasma DPP-IV activity and presumably the subsequent increase in endogenous incretin action.